Particle Simulation of Oxidation Induced Band 3 Clustering in Human Erythrocytes

Hanae Shimo, Satya Nanda Vel Arjunan, Hiroaki Machiyama, Taiko Nishino, Makoto Suematsu, Hideaki Fujita, Masaru Tomita, Koichi Takahashi

研究成果: Article査読

19 被引用数 (Scopus)


Oxidative stress mediated clustering of membrane protein band 3 plays an essential role in the clearance of damaged and aged red blood cells (RBCs) from the circulation. While a number of previous experimental studies have observed changes in band 3 distribution after oxidative treatment, the details of how these clusters are formed and how their properties change under different conditions have remained poorly understood. To address these issues, a framework that enables the simultaneous monitoring of the temporal and spatial changes following oxidation is needed. In this study, we established a novel simulation strategy that incorporates deterministic and stochastic reactions with particle reaction-diffusion processes, to model band 3 cluster formation at single molecule resolution. By integrating a kinetic model of RBC antioxidant metabolism with a model of band 3 diffusion, we developed a model that reproduces the time-dependent changes of glutathione and clustered band 3 levels, as well as band 3 distribution during oxidative treatment, observed in prior studies. We predicted that cluster formation is largely dependent on fast reverse reaction rates, strong affinity between clustering molecules, and irreversible hemichrome binding. We further predicted that under repeated oxidative perturbations, clusters tended to progressively grow and shift towards an irreversible state. Application of our model to simulate oxidation in RBCs with cytoskeletal deficiency also suggested that oxidation leads to more enhanced clustering compared to healthy RBCs. Taken together, our model enables the prediction of band 3 spatio-temporal profiles under various situations, thus providing valuable insights to potentially aid understanding mechanisms for removing senescent and premature RBCs.

ジャーナルPLoS Computational Biology
出版ステータスPublished - 2015 6月 5

ASJC Scopus subject areas

  • 生態、進化、行動および分類学
  • モデリングとシミュレーション
  • 生態学
  • 分子生物学
  • 遺伝学
  • 細胞および分子神経科学
  • 計算理論と計算数学


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